The generation, differentiation, and specializations of osteoclasts in bone resorption are not well understood. We propose to carefully examine and later exploit a system where rapid changes in osteoclast activity are suspected to occur. During egg-laying birds, osteoclasts resorb medullary bone calcium for egg shell formation. Quantitative population analysis indicates no change in osteoclast populations during the egg cycle. This data argues against rapid modulation of bone cells as has been suggested. Preliminary structural and ultrastructural data suggests that medullary bone osteoclasts go through synchronized functional changes rather than population changes during the egg cycle. We propose to characterize this unique physiological system of osteoclast "activation" and "inactivation" by using microscopy, autoradiography, electron microscopy, and histochemistry. We propose to utilize this unique system to examine specific effects of agents on osteoclast structure and function. Initially the effects of parathyroid hormone on osteoclast "activation" will be studied using quantitative morphometrics at the light and electron microscope levels. Parameters to be studied include recruitment off osteoclast nuclei, generation of ruffled borders, role of the filamentous zone, and synthesis and release of lysosomal enzymes. Once sufficient baselines are established, and the endocrine system of the bird can be managed, the effects of other agents, like vitamin D metabolites, calcitonin, endotoxins, dental plaque antigens, etc. will be examined on synchronized osteoclast populations. Feasibility of using this system in vitro will be tested.